ArticleThe Journal of biological chemistry2012
Protein kinase Cα (PKCα) regulates p53 localization and melanoma cell survival downstream of integrin αv in three-dimensional collagen and in vivo.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- PKCα regulates the secretion of PDL1-carrying small extracellular vesicles in a p53-dependent manner.Cell death & disease · 2025Article
- Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Oestrogen Receptor Isoforms May Represent a Therapeutic Target in Oesophageal Adenocarcinoma.Cancers · 2022Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- PKCα is required for Akt-mTORC1 activation in non-small cell lung carcinoma (NSCLC) with EGFR mutation.Oncogene · 2019Article
- Protein kinase C-α is upregulated by IMP1 in melanoma and is linked to poor survival.Melanoma research · 2019Article
- The role of collagen in cancer: from bench to bedside.Journal of translational medicine · 2019Review
- Investigation of the DNA damage response to SFOM-0046, a new small-molecule drug inducing DNA double-strand breaks.Scientific reports · 2016Article
- Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line.Molecular biology reports · 2015Article
- Dynamics and Membrane Interactions of Protein Kinase C.Biochemistry · 2015Review
- Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis.Oncology reports · 2015Article
- Reduction of protein kinase C α (PKC-α) promote apoptosis via down-regulation of Dicer in bladder cancer.Journal of cellular and molecular medicine · 2015Article
- p53 in cell invasion, podosomes, and invadopodia.Cell adhesion & migration · 2014Review
- Integrins and p53 pathways in glioblastoma resistance to temozolomide.Frontiers in oncology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase C α (PKCα) is overexpressed in numerous types of cancer. Importantly, PKCα has been linked to metastasis of malignant melanoma in patients. However, it has been unclear how PKCα may be regulated and how it exerts its role in melanoma. Here, we identified a role for PKCα in melanoma cell survival in a three-dimensional collagen model mimicking the in vivo pathophysiology of the dermis. A pathway was identified that involved integrin αv-mediated up-regulation of PKCα and PKCα-dependent regulation of p53 localization, which was connected to melanoma cell survival. Melanoma survival and growth in three-dimensional microenvironments requires the expression of integrin αv, which acts to suppress p53 activity. Interestingly, microarray analysis revealed that PKCα was up-regulated by integrin αv in a three-dimensional microenvironment-dependent manner. Integrin αv was observed to promote a relocalization of endogenous p53 from the nucleus to the cytoplasm upon growth in three-dimensional collagen as well as in vivo, whereas stable knockdown of PKCα inhibited the integrin αv-mediated relocalization of p53. Importantly, knockdown of PKCα also promoted apoptosis in three-dimensional collagen and in vivo, resulting in reduced tumor growth. This indicates that PKCα constitutes a crucial component of the integrin αv-mediated pathway(s) that promote p53 relocalization and melanoma survival.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.